3zzy: Difference between revisions

Latest revision as of 11:17, 20 December 2023

Crystal structure of a Raver1 PRI3 peptide in complex with polypyrimidine tract binding protein RRM2

Structural highlights

3zzy is a 4 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.4Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PTBP1_HUMAN Plays a role in pre-mRNA splicing and in the regulation of alternative splicing events. Activates exon skipping of its own pre-mRNA during muscle cell differentiation. Binds to the polypyrimidine tract of introns. May promote RNA looping when bound to two separate polypyrimidine tracts in the same pre-mRNA. May promote the binding of U2 snRNP to pre-mRNA. Cooperates with RAVER1 to modulate switching between mutually exclusive exons during maturation of the TPM1 pre-mRNA. Represses the splicing of MAPT/Tau exon 10.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

The polypyrimidine tract-binding protein (PTB) is an important regulator of alternative splicing. PTB-regulated splicing of alpha-tropomyosin is enhanced by Raver1, a protein with four PTB-Raver1 interacting motifs (PRIs) that bind to the helical face of the second RNA recognition motif (RRM2) in PTB. We present the crystal structures of RRM2 in complex with PRI3 and PRI4 from Raver1, which-along with structure-based mutagenesis-reveal the molecular basis of their differential binding. High-affinity binding by Raver1 PRI3 involves shape-matched apolar contacts complemented by specific hydrogen bonds, a new variant of an established mode of peptide-RRM interaction. Our results refine the sequence of the PRI motif and place important structural constraints on functional models of PTB-Raver1 interactions. Our analysis indicates that the observed Raver1-PTB interaction is a general mode of binding that applies to Raver1 complexes with PTB paralogues such as nPTB and to complexes of Raver2 with PTB.

Crystallographic analysis of polypyrimidine tract-binding protein-raver1 interactions involved in regulation of alternative splicing.,Joshi A, Coelho MB, Kotik-Kogan O, Simpson PJ, Matthews SJ, Smith CW, Curry S Structure. 2011 Dec 7;19(12):1816-25. PMID:22153504^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Markovtsov V, Nikolic JM, Goldman JA, Turck CW, Chou MY, Black DL. Cooperative assembly of an hnRNP complex induced by a tissue-specific homolog of polypyrimidine tract binding protein. Mol Cell Biol. 2000 Oct;20(20):7463-79. PMID:11003644
↑ Wang J, Gao QS, Wang Y, Lafyatis R, Stamm S, Andreadis A. Tau exon 10, whose missplicing causes frontotemporal dementia, is regulated by an intricate interplay of cis elements and trans factors. J Neurochem. 2004 Mar;88(5):1078-90. PMID:15009664
↑ Lin JC, Tarn WY. Exon selection in alpha-tropomyosin mRNA is regulated by the antagonistic action of RBM4 and PTB. Mol Cell Biol. 2005 Nov;25(22):10111-21. PMID:16260624 doi:https://dx.doi.org/10.1128/MCB.25.22.10111-10121.2005
↑ Lin JC, Tarn WY. RBM4 down-regulates PTB and antagonizes its activity in muscle cell-specific alternative splicing. J Cell Biol. 2011 May 2;193(3):509-20. doi: 10.1083/jcb.201007131. Epub 2011 Apr , 25. PMID:21518792 doi:https://dx.doi.org/10.1083/jcb.201007131
↑ Oberstrass FC, Auweter SD, Erat M, Hargous Y, Henning A, Wenter P, Reymond L, Amir-Ahmady B, Pitsch S, Black DL, Allain FH. Structure of PTB bound to RNA: specific binding and implications for splicing regulation. Science. 2005 Sep 23;309(5743):2054-7. PMID:16179478 doi:https://dx.doi.org/309/5743/2054
↑ Joshi A, Coelho MB, Kotik-Kogan O, Simpson PJ, Matthews SJ, Smith CW, Curry S. Crystallographic analysis of polypyrimidine tract-binding protein-raver1 interactions involved in regulation of alternative splicing. Structure. 2011 Dec 7;19(12):1816-25. PMID:22153504 doi:10.1016/j.str.2011.09.020

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OCA

[1] Markovtsov V, Nikolic JM, Goldman JA, Turck CW, Chou MY, Black DL. Cooperative assembly of an hnRNP complex induced by a tissue-specific homolog of polypyrimidine tract binding protein. Mol Cell Biol. 2000 Oct;20(20):7463-79. PMID:11003644

[2] Wang J, Gao QS, Wang Y, Lafyatis R, Stamm S, Andreadis A. Tau exon 10, whose missplicing causes frontotemporal dementia, is regulated by an intricate interplay of cis elements and trans factors. J Neurochem. 2004 Mar;88(5):1078-90. PMID:15009664

[3] Lin JC, Tarn WY. Exon selection in alpha-tropomyosin mRNA is regulated by the antagonistic action of RBM4 and PTB. Mol Cell Biol. 2005 Nov;25(22):10111-21. PMID:16260624 doi:https://dx.doi.org/10.1128/MCB.25.22.10111-10121.2005

[4] Lin JC, Tarn WY. RBM4 down-regulates PTB and antagonizes its activity in muscle cell-specific alternative splicing. J Cell Biol. 2011 May 2;193(3):509-20. doi: 10.1083/jcb.201007131. Epub 2011 Apr , 25. PMID:21518792 doi:https://dx.doi.org/10.1083/jcb.201007131

[5] Oberstrass FC, Auweter SD, Erat M, Hargous Y, Henning A, Wenter P, Reymond L, Amir-Ahmady B, Pitsch S, Black DL, Allain FH. Structure of PTB bound to RNA: specific binding and implications for splicing regulation. Science. 2005 Sep 23;309(5743):2054-7. PMID:16179478 doi:https://dx.doi.org/309/5743/2054

[6] Joshi A, Coelho MB, Kotik-Kogan O, Simpson PJ, Matthews SJ, Smith CW, Curry S. Crystallographic analysis of polypyrimidine tract-binding protein-raver1 interactions involved in regulation of alternative splicing. Structure. 2011 Dec 7;19(12):1816-25. PMID:22153504 doi:10.1016/j.str.2011.09.020

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@@ Line 1: / Line 1: @@
 ==Crystal structure of a Raver1 PRI3 peptide in complex with polypyrimidine tract binding protein RRM2==
-<StructureSection load='3zzy' size='340' side='right' caption='[[3zzy]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
+<StructureSection load='3zzy' size='340' side='right'caption='[[3zzy]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3zzy]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZZY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZZY FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3zzy]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZZY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZZY FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1qm9|1qm9]], [[1sjr|1sjr]], [[2adb|2adb]], [[2ad9|2ad9]], [[2adc|2adc]], [[2evz|2evz]], [[1sjq|1sjq]], [[1wi6|1wi6]], [[3zzz|3zzz]]</td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.4&#8491;</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3zzy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zzy OCA], [http://pdbe.org/3zzy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3zzy RCSB], [http://www.ebi.ac.uk/pdbsum/3zzy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3zzy ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3zzy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zzy OCA], [https://pdbe.org/3zzy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zzy RCSB], [https://www.ebi.ac.uk/pdbsum/3zzy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zzy ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/PTBP1_HUMAN PTBP1_HUMAN]] Plays a role in pre-mRNA splicing and in the regulation of alternative splicing events. Activates exon skipping of its own pre-mRNA during muscle cell differentiation. Binds to the polypyrimidine tract of introns. May promote RNA looping when bound to two separate polypyrimidine tracts in the same pre-mRNA. May promote the binding of U2 snRNP to pre-mRNA. Cooperates with RAVER1 to modulate switching between mutually exclusive exons during maturation of the TPM1 pre-mRNA. Represses the splicing of MAPT/Tau exon 10.<ref>PMID:11003644</ref> <ref>PMID:15009664</ref> <ref>PMID:16260624</ref> <ref>PMID:21518792</ref> <ref>PMID:16179478</ref>  [[http://www.uniprot.org/uniprot/RAVR1_MOUSE RAVR1_MOUSE]] Cooperates with PTBP1 to modulate regulated alternative splicing events. Promotes exon skipping. Cooperates with PTBP1 to modulate switching between mutually exclusive exons during maturation of the TPM1 pre-mRNA.<ref>PMID:14633994</ref>
+[https://www.uniprot.org/uniprot/PTBP1_HUMAN PTBP1_HUMAN] Plays a role in pre-mRNA splicing and in the regulation of alternative splicing events. Activates exon skipping of its own pre-mRNA during muscle cell differentiation. Binds to the polypyrimidine tract of introns. May promote RNA looping when bound to two separate polypyrimidine tracts in the same pre-mRNA. May promote the binding of U2 snRNP to pre-mRNA. Cooperates with RAVER1 to modulate switching between mutually exclusive exons during maturation of the TPM1 pre-mRNA. Represses the splicing of MAPT/Tau exon 10.<ref>PMID:11003644</ref> <ref>PMID:15009664</ref> <ref>PMID:16260624</ref> <ref>PMID:21518792</ref> <ref>PMID:16179478</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 22: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Lk3 transgenic mice]]
+[[Category: Large Structures]]
-[[Category: Curry, S]]
+[[Category: Mus musculus]]
-[[Category: Joshi, A]]
+[[Category: Curry S]]
-[[Category: Kotik-Kogan, O]]
+[[Category: Joshi A]]
-[[Category: Peptide binding]]
+[[Category: Kotik-Kogan O]]
-[[Category: Protein binding]]
-[[Category: Rna recognition motif]]

3zzy: Difference between revisions

Latest revision as of 11:17, 20 December 2023

Crystal structure of a Raver1 PRI3 peptide in complex with polypyrimidine tract binding protein RRM2

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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